tbuckley/cabot-search huggingface dataset:
TRIM67 drives tumorigenesis in oligodendrogliomas through Rho GTPase-dependent membrane blebbing
Authors: Engin Demirdizen, Ruslan Al-Ali, Ashwin Narayanan, Xueyuan Sun, Julianna Patricia Varga, Bianca Steffl, Manuela Brom, Damir Krunic, Claudia Schmidt, Gabriele Schmidt, Felix Bestvater, Julian Taranda, Şevin Turcan
Journal: Neuro-Oncology (2022)

IDH mutant gliomas are grouped into astrocytomas or oligodendrogliomas depending on the codeletion of chromosome arms 1p and 19q. Although the genomic alterations of IDH mutant gliomas have been well described, transcriptional changes unique to either tumor type have not been fully understood. Here, we identify Tripartite Motif Containing 67 (TRIM67), an E3 ubiquitin ligase with essential roles during neuronal development, as an oncogene distinctly upregulated in oligodendrogliomas.We used several cell lines, including patient-derived oligodendroglioma tumorspheres, to knock down or overexpress TRIM67. We coupled high-throughput assays, including RNA sequencing, total lysate-mass spectrometry (MS), and coimmunoprecipitation (co-IP)-MS with functional assays including immunofluorescence (IF) staining, co-IP, and western blotting (WB) to assess the in vitro phenotype associated with TRIM67. Patient-derived oligodendroglioma tumorspheres were orthotopically implanted in mice to determine the effect of TRIM67 on tumor growth and survival.TRIM67 overexpression alters the abundance of cytoskeletal proteins and induces membrane bleb formation. TRIM67-associated blebbing was reverted with the nonmuscle class II myosin inhibitor blebbistatin and selective ROCK inhibitor fasudil. NOGO-A/Rho GTPase/ROCK2 signaling is altered upon TRIM67 ectopic expression, pointing to the underlying mechanism for TRIM67-induced blebbing. Phenotypically, TRIM67 expression resulted in higher cell motility and reduced cell adherence. In orthotopic implantation models of patient-derived oligodendrogliomas, TRIM67 accelerated tumor growth, reduced overall survival, and led to increased vimentin expression at the tumor margin.Taken together, our results demonstrate that upregulated TRIM67 induces blebbing-based rounded cell morphology through Rho GTPase/ROCK-mediated signaling thereby contributing to glioma pathogenesis.
Hydrogel-Based Stimuli-Responsive Micromotors for Biomedicine
Authors: Huaijuan Zhou, Guozhao Dong, Ge Gao, Ran Du, Xiaoying Tang, Yining Ma, Jinhua Li
Journal: Cyborg and Bionic Systems (2022)

The rapid development of medical micromotors draws a beautiful blueprint for the noninvasive or minimally invasive diagnosis and therapy. By combining stimuli-sensitive hydrogel materials, micromotors are bestowed with new characteristics such as stimuli-responsive shape transformation/morphing, excellent biocompatibility and biodegradability, and drug loading ability. Actuated by chemical fuels or external fields (e.g., magnetic field, ultrasound, light, and electric field), hydrogel-based stimuli-responsive (HBSR) micromotors can be utilized to load therapeutic agents into the hydrogel networks or directly grip the target cargos (e.g., drug-loaded particles, cells, and thrombus), transport them to sites of interest (e.g., tumor area and diseased tissues), and unload the cargos or execute a specific task (e.g., cell capture, targeted sampling, and removal of blood clots) in response to a stimulus (e.g., change of temperature, pH, ion strength, and chemicals) in the physiological environment. The high flexibility, adaptive capacity, and shape morphing property enable the HBSR micromotors to complete specific medical tasks in complex physiological scenarios, especially in confined, hard-to-reach tissues, and vessels of the body. Herein, this review summarizes the current progress in hydrogel-based medical micromotors with stimuli responsiveness. The thermo-responsive, photothermal-responsive, magnetocaloric-responsive, pH-responsive, ionic-strength-responsive, and chemoresponsive micromotors are discussed in detail. Finally, current challenges and future perspectives for the development of HBSR micromotors in the biomedical field are discussed.
Bile peritonitis after placement of a metallic stent in endoscopic ultrasound-guided hepaticogastrostomy: A pitfall and the rescue technique
Authors: Akihisa Ohno, Nao Fujimori, Toshiya Abe, Masafumi Nakamura, Yoshihiro Ogawa
Journal: Endoscopy (2022)

The complications of endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) are different from those of endoscopic retrograde cholangiopancreatography (ERCP). Among these, bile peritonitis can be fatal, and insertion of a metallic stent is recommended to prevent this complication [1]. There have been a few reports about bile peritonitis after EUS-HGS [2] [3]. We report a rare case of bile peritonitis which occurred immediately after the placement of a metallic stent, and the rescue technique.
A release from WONderland: endoscopic ultrasonography-guided reconnection of disconnected pancreatic ducts across a walled-off necrosis cavity
Authors: Tatsuya Sato, Tomotaka Saito, Tsuyoshi Hamada, Yousuke Nakai, Mitsuhiro Fujishiro
Journal: Endoscopy (2022)

Disconnected pancreatic duct syndrome (DPDS) in cases with walled-off necrosis (WON) is associated with recurrence of pancreatic fluid collection [1] and new-onset diabetes [2]. Transpapillary stent placement across disconnected pancreas has been attempted but the technical success rate of this procedure is low [3] [4].
Miniprobe ultrasonography guidance during endoscopic submucosal dissection of an ampullary duodenal lesion
Authors: Yuki Nakajima, Daiki Nemoto, Kohei Suzuki, Ai Sato, Goro Shibukawa, Alan Kawarai Lefor, Kazutomo Togashi
Journal: Endoscopy (2022)

Endoscopic submucosal dissection (ESD) of ampullary lesions is an alternative to endoscopic papillectomy [1], which has several drawbacks such as a significant perforation rate, bleeding, and a low curative resection rate [2] [3] [4]. ESD may overcome these drawbacks, except for the risk of perforation. The sphincter of Oddi often cannot be distinguished from the duodenal muscularis. We report a novel technique using miniprobe ultrasonography to identify the sphincter of Oddi, which facilitates appropriate dissection just above the muscularis propria.
Metal stenting for caustic esophageal injury with bronchoesophageal fistula
Authors: Mark H. Bonnichsen, Jack McNamara, Goktug Ermerak, Yasser Farooque, Milan Bassan
Journal: Endoscopy (2022)

A 68-year-old woman presented after intentional ingestion of a pH 11 caustic solution (sodium hypochlorite and sodium hydroxide). Urgent gastroscopy showed severe distal esophageal stricturing with Zargar IIA injury [1] that could not be traversed with a standard gastroscope ([Fig. 1]). A computed tomography (CT) scan did not show evidence of esophageal perforation.
Intensive endoscopic resection for downstaging of polyp burden in patients with familial adenomatous polyposis (J-FAPP Study III): a multicenter prospective interventional study
Authors: Hideki Ishikawa, Masayoshi Yamada, Yasushi Sato, Shinji Tanaka, Chino Akiko, Masahiro Tajika, Hisashi Doyama, Tetsuji Takayama, Yoshio Ohda, Takahiro Horimatsu, Yasushi Sano, Kohji Tanakaya, Hiroaki Ikematsu, Yoshihisa Saida, Hideyuki Ishida, Yoji Takeuchi, Hiroshi Kashida, Shinsuke Kiriyama, Shinichiro Hori, Kyowon Lee, Jun Tashiro, Nozomu Kobayashi, Takeshi Nakajima, Sadao Suzuki, Michihiro Mutoh
Journal: Endoscopy (2022)

Total colectomy is the standard treatment for familial adenomatous polyposis (FAP). Recently, an increasing number of young patients with FAP have requested the postponement of surgery or have refused to undergo surgery. We aimed to evaluate the effectiveness of intensive endoscopic removal for downstaging of polyp burden (IDP) in FAP.A single-arm intervention study was conducted at 22 facilities. Participants were patients with FAP, aged ≥ 16 years, who had not undergone colectomy or who had undergone colectomy but had ≥ 10 cm of large intestine remaining. For IDP, colorectal polyps of ≥ 10 mm were removed, followed by polyps of ≥ 5 mm. The primary end point was the presence/absence of colectomy during a 5-year intervention period.222 patients were eligible, of whom 166 had not undergone colectomy, 46 had undergone subtotal colectomy with ileorectal anastomosis, and 10 had undergone partial resection of the large intestine. During the intervention period, five patients (2.3 %, 95 % confidence interval [CI] 0.74 %-5.18 %) underwent colectomy, and three patients died. Completion of the 5-year intervention period without colectomy was confirmed in 150 /166 patients who had not undergone colectomy (90.4 %, 95 %CI 84.8 %-94.4 %) and in 47 /56 patients who had previously undergone colectomy (83.9 %, 95 %CI 71.7 %-92.4 %).IDP in patients with mild-to-moderate FAP could have the potential to be a useful means of preventing colorectal cancer without implementing colectomy. However, if the IDP protocol was proposed during a much longer term, it may not preclude the possibility that a large proportion of colectomies may still need to be performed.
Endoluminal hemostasis of a Dieulafoy-like lesion of the gallbladder after endoscopic ultrasound-guided biliary drainage by a lumen-apposing stent
Authors: Antoine Debourdeau, Jules Daniel, Jean Goupil, Mathilde Sanavio, Philippe Pouderoux, Jean-François Bourgaux, Ludovic Caillo
Journal: Endoscopy (2022)

A 57-year-old woman presented to our unit for jaundice related to pancreatic cancer with a previously stented duodenal stricture. As the duodenal papilla or choledochus was not reachable, endoscopic ultrasound (EUS)-guided gallbladder biliary drainage was achieved by cholecystogastrostomy with a lumen-apposing metal stent (LAMS) (Axios 10 mm; Boston Scientific, Marlborough, Massachusetts, USA).
Update on the investigation into the publication record of former<i>BJSM</i>editor-in-chief Paul McCrory
Authors: Helen Macdonald, Simone Ragavooloo, Kamran Abbasi, Jonathan A Drezner
Journal: British Journal of Sports Medicine (2022)

<h3>ABSTRACT</h3> Each additional copy of the apolipoprotein E4 (APOE4) allele is associated with a higher risk of Alzheimer’s dementia, such that APOE4 homozygotes have a particularly high risk. While the APOE2 allele is associated with a lower risk of Alzheimer’s dementia, it is not yet known whether APOE2 homozygotes have a particularly low risk. We generated Alzheimer’s dementia odds ratios and other findings in more than 5,000 clinically characterized and neuropathologically characterized Alzheimer’s dementia cases and controls. APOE2/2 was associated with exceptionally low Alzheimer’s dementia odds ratios compared to APOE2/3, 3/3 and 4/4, and the impact of APOE2 and APOE4 gene dose was significantly greater in the neuropathologically confirmed group than in more than 24,000 neuropathologically unconfirmed cases and controls. Finding and targeting the factors by which APOE and its variants influence Alzheimer’s disease could have a major impact on the understanding, treatment and prevention of this terrible disease.
Closure of full-thickness perforations in porcine stomach using 20-mm reopenable clips
Authors: Tatsuma Nomura, Shinya Sugimoto, Haruka Nakamura, Jun Oyamada, Keiichi Ito, Akira Kamei
Journal: Endoscopy (2022)

It is difficult to close perforations that are large and full thickness in the gastrointestinal tract using conventional clips. Closure methods using special devices, including the over-the-scope (OTS) clip (Ovesco, Tübingen, Germany), have therefore been devised [1] [2] [3]. However, the OTS clip cannot be regripped and cannot be used unless the endoscope is pulled out for the clip to be attached [4]. Therefore, a device that can reliably close a perforation under endoscopic visibility is desired. We introduce a reopenable clip, which has a large width of 20 mm, and demonstrate its ability to close large gastric perforations in a porcine model.
Gel-immersion electrohydraulic lithotripsy during digital single-operator cholangioscopy is helpful when bleeding occurs
Authors: Akira Miyano, Takeshi Ogura, Atsushi Okuda, Nobu Nishioka, Hiroki Nishikawa
Journal: Endoscopy (2022)

Electrohydraulic lithotripsy (EHL) during digital single-operator cholangioscopy (dSOC) is a useful technique for difficult bile duct stones [1] [2]; however, visibility during dSOC can be poor in the presence of bleeding or infected bile juice. In such situations, EHL may be challenging. The use of gel-immersion endoscopy using a transparent gel (Viscoclear; Otsuka Pharmaceutical Factory, Tokushima, Japan), which is more viscous than saline ([Fig. 1]), has recently been reported as a method for securing the visual field [3] [4] [5]. Use of the gel-immersion technique has not yet been reported in the pancreaticobiliary endoscopic field. We herein describe technical tips for gel-immersion EHL during dSOC for bile duct stones.
Superficial nonampullary duodenal epithelial tumor: a rare case with signet-ring cell carcinoma component diagnosed by magnifying endoscopy
Authors: Takashi Muramoto, Ken Ohata, Syunya Takayanagi, Yoshiaki Kimoto, Rindo Ishii, Ryoju Negishi, Yohei Minato
Journal: Endoscopy (2022)

A 73-year-old man was referred to our hospital for treatment of a superficial nonampullary duodenal epithelial tumor (SNADET). The tumor was a reddish and depressed lesion in the center, measuring 10 mm in diameter, and located in the superior duodenal angle ([Fig. 1 a, b]). Magnifying endoscopy with narrow-band imaging (ME-NBI) showed a disappearance of microsurface pattern and irregular corkscrew microvascular pattern on the surface within the depressed area ([Fig. 1 c]). Subsequently, the lesion was stained with a mixture of 0.05 % crystal violet and 0.1 % methylene blue, followed by endocytoscopic observation. Endocytoscopy showed no formation of glandular lumen, only nuclear swelling visualized with methylene blue ([Fig. 1 d]). We diagnosed SNADET with a component of signet-ring cell carcinoma, and endoscopic submucosal dissection (ESD) was planned for the purpose of en bloc resection.
The role of macroscopic on-site evaluation in the era of biopsy needles: is it still useful?
Authors: Hirotoshi Ishiwatari
Journal: Endoscopy (2022)

Macroscopic on-site evaluation (MOSE) involves visual assessment of samples obtained during endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). In brief, the presence or length of the macroscopically visible core is investigated to decide whether an appropriate sample for pathological evaluation has been obtained [1] [2]. The approach is similar to that of rapid on-site evaluation (ROSE), which differs from MOSE in terms of cytological evaluation. ROSE overcomes the disadvantage of EUS-FNA, in which more than three or four needle passes are required for sufficient diagnostic accuracy, by reducing the number of needle passes [3]. However, because of limited pathology staffing, ROSE has not been implemented in many hospitals, especially in Europe and Asia. MOSE may therefore be an alternative in such situations [1] [2].
Self-expandable metallic stent deployment across the ileocecal valve in a patient with an acute colonic obstruction
Authors: Takuya Takahama, Tesshin Ban, Yoshimasa Kubota, Tsuyoshi Itoh, Makoto Nakamura, Takashi Joh
Journal: Endoscopy (2022)

Although self-expandable metallic stent (SEMS) deployment is a treatment option for proximal malignant colonic obstructions, it remains a challenging procedure [1] [2] [3]. When the malignant colonic obstruction is close to the ileocecal valve, it is impossible to maintain a 2.0 cm safety margin on the oral end of the SEMS [1] [2] [3]. This article describes the deployment of SEMS across the ileocecal valve in a patient with acute malignant colonic obstruction.
Use of texture and color enhancement imaging to identify the pancreatic duct orifice in a patient with a pancreaticojejunal anastomotic stricture
Authors: Yuki Tanisaka, Masafumi Mizuide, Akashi Fujita, Rie Shiomi, Takahiro Shin, Dai Hirata, Shomei Ryozawa
Journal: Endoscopy (2022)

An endoscopic approach to pancreaticojejunal anastomotic stricture (PJAS) using a balloon enteroscope in patients who have undergone pancreaticoduodenectomy is challenging [1] [2] [3]. Identification of the pancreatic duct orifice is often difficult because of complete PJAS. Herein, we report the case of a patient with a PJAS in whom a texture and color enhancement imaging (TXI)-equipped new-generation endoscopy system (EVIS X1; Olympus Medical Systems, Japan) [4] was used, which facilitated identification of the pancreatic duct orifice.
Cystic duct stump stone removal by retrieval basket under direct visualization using a novel peroral choledochoscope
Authors: Wen-Lin Zhang, Rui Ji
Journal: Endoscopy (2022)

Calculus in a cystic duct remnant is one of the causes of postcholecystectomy syndrome. Surgical extraction of the stone with excision of the cystic duct can be carried out, but the adhesions caused by the prior operation make the reoperation more challenging [1]. Endoscopic retrograde cholangiopancreatography (ERCP) has been used to extract the stone in combination with lithotripsy [2] [3] [4], but is confined to only a small subset of patients. We present a novel peroral choledochoscope (Eye-Max CDS11001; Micro-Tech, China) with a 1.8-mm working channel to introduce therapeutic equipment ([Fig. 1]).
Planetary health: Five minutes with…Oisín Brady Bates
Authors: Elisabeth Mahase
Journal: BMJ (2022)

<h3>Objective:</h3> To explore the underlying reasons of dizziness experienced by patients after having the COVID-19 infections or vaccinations. <h3>Background:</h3> At our dizziness center, we saw a spike of dizziness consults after patients were diagnosed with COVID-19 infections or received COVID-19 vaccinations. The symptoms included dizziness, vertigo, and imbalance. This study aims to examine if the infection, vaccination, or antibodies from such could be the reason for the dizziness complaints or if other factors explain patients’ dizziness. <h3>Design/Methods:</h3> Patients were identified using a combination of retrospective chart review to identify patients with diagnoses of dizziness, COVID-19, and COVID-19 vaccinations from our database, coupled with referrals from ongoing clinical consultations who we believed to exhibit dizziness symptoms related to their COVID-19 infections or vaccinations within four weeks of dizziness onset. Patients all had brain MRI and extensive vestibular testing, including: VNG, Rotary Chair, audiograms, and consultation with an experienced neuro-otologist. <h3>Results:</h3> Of the 40 patients examined, 20 began experiencing dizziness after testing positive for COVID-19 and 20 reported dizziness after receiving the vaccines. All patients had brain MRI, but no MRI findings indicated inflammatory changes from infections or antibody reactions. Only five of 40 patients had abnormal VNG indications of uncompensated peripheral vestibulopathy which could be related to virus infections or antibody reactions. Thirty out of 40 patients had histories of anxiety, depression, other mood disorders, or family histories of mood disorders. Based on the clinical history and examinations, along with MRI findings and comprehensive vestibular testing, 75% of the 40 patients had diagnoses of persistent perceptual positional vertigo (PPPV), which was most likely related to patients’ underlying anxiety, depression, or mood disorders. <h3>Conclusions:</h3> We believe that the COVID-19 infections or vaccinations may trigger PPPV as stressors, but mostly not due to the virus infections or its antibody reactions. <b>Disclosure:</b> Mr. Kahn has received personal compensation for serving as an employee of DENT Neurologic Institute. Ms. Stephenson has nothing to disclose. Dr. Cox has nothing to disclose. Dr. Zhang has nothing to disclose.
Comparison of emergency surgical cricothyroidotomy and percutaneous cricothyroidotomy by experienced airway providers in an obese, in vivo porcine hemorrhage airway model
Authors: Tomas Karlsson, Andreas Brännström, Mikael Gellerfors, Jenny Gustavsson, Mattias Günther
Journal: Military Medical Research (2022)

Emergency front-of-neck airway (eFONA) is a life-saving procedure in "cannot intubate, cannot oxygenate" (CICO). The fastest and most reliable method of eFONA has not been determined. We compared two of the most advocated approaches: surgical cricothyroidotomy and percutaneous cricothyroidotomy, in an obese, in vivo porcine hemorrhage model, designed to introduce real-time physiological feedback, relevant and high provider stress. The primary aim was to determine the fastest method to secure airway. Secondary aims were arterial saturation and partial pressure of oxygen, proxy survival and influence of experience. Twelve pigs, mean weight (standard deviation, SD) (60.3 ± 4.1) kg, were anesthetized and exposed to 25-35% total blood volume hemorrhage before extubation and randomization to Seldinger technique "percutaneous cricothyroidotomy" (n = 6) or scalpel-bougie-tube technique "surgical cricothyroidotomy" (n = 6). Specialists in anesthesia and intensive care in a tertiary referral hospital performed the eFONA, simulating an actual CICO-situation. In surgical cricothyroidotomy vs. percutaneous cricothyroidotomy, the median (interquartile range, IQR) times to secure airway were 109 (IQR 71-130) s and 298 (IQR 128-360) s (P = 0.0152), arterial blood saturation (SaO2) were 74.7 (IQR 46.6-84.2) % and 7.9 (IQR 4.1-15.6) % (P = 0.0167), pO2 were 7.0 (IQR 4.7-7.7) kPa and 2.0 (IQR 1.1-2.9) kPa (P = 0.0667), and times of cardiac arrest (proxy survival) were 137-233 s, 190 (IQR 143-229), from CICO. All six animals survived surgical cricothyroidotomy, and two of six (33%) animals survived percutaneous cricothyroidotomy. Years in anesthesia, 13.5 (IQR 7.5-21.3), did not influence time to secure airway. eFONA by surgical cricothyroidotomy was faster and had increased oxygenation and survival, when performed under stress by board certified anesthesiologists, and may be an indication of preferred method in situations with hemorrhage and CICO, in obese patients.
Structural diversification of bioactive bibenzyls through modular co-culture leading to the discovery of a novel neuroprotective agent
Authors: Yuyu Liu, Xinnan Li, Songyang Sui, Jingshu Tang, Dawei Chen, Yuying Kang, Kebo Xie, Jimei Liu, Jiaqi Lan, Lei Wu, Ridao Chen, Ying Peng, Jungui Dai
Journal: Acta Pharmaceutica Sinica B (2022)

Bibenzyls, a kind of important plant polyphenols, have attracted growing attention for their broad and remarkable pharmacological activities. However, due to the low abundance in nature, uncontrollable and environmentally unfriendly chemical synthesis processes, these compounds are not readily accessible. Herein, one high-yield bibenzyl backbone-producing Escherichia coli strain was constructed by using a highly active and substrate-promiscuous bibenzyl synthase identified from Dendrobium officinale in combination with starter and extender biosynthetic enzymes. Three types of efficiently post-modifying modular strains were engineered by employing methyltransferases, prenyltransferase, and glycosyltransferase with high activity and substrate tolerance together with their corresponding donor biosynthetic modules. Structurally different bibenzyl derivatives were tandemly and/or divergently synthesized by co-culture engineering in various combination modes. Especially, a prenylated bibenzyl derivative (12) was found to be an antioxidant that exhibited potent neuroprotective activity in the cellular and rat models of ischemia stroke. RNA-seq, quantitative RT-PCR, and Western-blot analysis demonstrated that 12 could up-regulate the expression level of an apoptosis-inducing factor, mitochondria associated 3 (Aifm3), suggesting that Aifm3 might be a new target in ischemic stroke therapy. This study provides a flexible plug-and-play strategy for the easy-to-implement synthesis of structurally diverse bibenzyls through a modular co-culture engineering pipeline for drug discovery.